Purification and characterization of active-site components of the putative p-cresol methylhydroxylase membrane complex from Geobacter metallireducens

J Bacteriol. 2008 Oct;190(19):6493-500. doi: 10.1128/JB.00790-08. Epub 2008 Jul 25.

Abstract

p-Cresol methylhydroxylases (PCMH) from aerobic and facultatively anaerobic bacteria are soluble, periplasmic flavocytochromes that catalyze the first step in biological p-cresol degradation, the hydroxylation of the substrate with water. Recent results suggested that p-cresol degradation in the strictly anaerobic Geobacter metallireducens involves a tightly membrane-bound PCMH complex. In this work, the soluble components of this complex were purified and characterized. The data obtained suggest a molecular mass of 124 +/- 15 kDa and a unique alphaalpha'beta(2) subunit composition, with alpha and alpha' representing isoforms of the flavin adenine dinucleotide (FAD)-containing subunit and beta representing a c-type cytochrome. Fluorescence and mass spectrometric analysis suggested that one FAD was covalently linked to Tyr(394) of the alpha subunit. In contrast, the alpha' subunit did not contain any FAD cofactor and is therefore considered to be catalytically inactive. The UV/visible spectrum was typical for a flavocytochrome with two heme c cofactors and one FAD cofactor. p-Cresol reduced the FAD but only one of the two heme cofactors. PCMH catalyzed both the hydroxylation of p-cresol to p-hydroxybenzyl alcohol and the subsequent oxidation of the latter to p-hydroxybenzaldehyde in the presence of artificial electron acceptors. The very low K(m) values (1.7 and 2.7 microM, respectively) suggest that the in vivo function of PCMH is to oxidize both p-cresol and p-hydroxybenzyl alcohol. The latter was a mixed inhibitor of p-cresol oxidation, with inhibition constants of a K(ic) (competitive inhibition) value of 18 +/- 9 microM and a K(iu) (uncompetitive inhibition) value of 235 +/- 20 microM. A putative functional model for an unusual PCMH enzyme is presented.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry
  • Bacterial Proteins / isolation & purification
  • Bacterial Proteins / metabolism*
  • Benzaldehydes / metabolism
  • Benzyl Alcohols / metabolism
  • Catalytic Domain
  • Chromatography, Gel
  • Chromatography, High Pressure Liquid
  • Chromatography, Liquid
  • Cresols / metabolism
  • Electrophoresis, Polyacrylamide Gel
  • Flavin-Adenine Dinucleotide / chemistry
  • Flavin-Adenine Dinucleotide / metabolism
  • Flavoproteins / chemistry
  • Flavoproteins / metabolism
  • Geobacter / enzymology*
  • Geobacter / metabolism
  • Heme / analogs & derivatives
  • Heme / chemistry
  • Heme / metabolism
  • Mass Spectrometry
  • Membrane Proteins / chemistry
  • Membrane Proteins / isolation & purification
  • Membrane Proteins / metabolism*
  • Mixed Function Oxygenases / chemistry
  • Mixed Function Oxygenases / isolation & purification
  • Mixed Function Oxygenases / metabolism*
  • Molecular Weight
  • Protein Isoforms / chemistry
  • Protein Isoforms / metabolism
  • Spectrophotometry, Ultraviolet

Substances

  • Bacterial Proteins
  • Benzaldehydes
  • Benzyl Alcohols
  • Cresols
  • Flavoproteins
  • Membrane Proteins
  • Protein Isoforms
  • Flavin-Adenine Dinucleotide
  • 4-hydroxybenzyl alcohol
  • heme C
  • Heme
  • Mixed Function Oxygenases
  • 4-cresol dehydrogenase (hydroxylating)
  • cresol
  • 4-hydroxybenzaldehyde